Comparison of Pitavastatin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus

NCT06767774 | Recruiting Phase 4 DMC

• 1 other identifier: AVOIDM
• Study Type: interventional
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

The AVOID-DM trial is a multicenter, prospective, randomized study comparing the risk of new-onset diabetes mellitus (DM) between two cholesterol-lowering strategies in patients with prediabetes and established atherosclerotic cardiovascular disease (ASCVD). The study evaluates pitavastatin plus ezetimibe combination therapy versus high-intensity statin monotherapy (rosuvastatin 20 mg). Enrolling 2,000 non-diabetic participants with ASCVD, subjects are randomized 1:1 into the two treatment arms. The primary outcome is the incidence of new-onset DM over a follow-up period of up to 36 months. Secondary outcomes include cardiovascular events, changes in LDL cholesterol, fasting glucose, HbA1c, and insulin resistance. This trial hypothesizes that the combination therapy will achieve LDL targets with a lower risk of new-onset DM compared to high-intensity statin monotherapy.

Conditions

ASCVD; Diabetes; Statin

Outcome Measures

Primary Outcomes (1)

• new-onset diabetes mellitus meeting diagnostic criteria for conventional diabetes during the treatment period

  3 years

Secondary Outcomes (1)

• 1. Composite of major clinical events of cardiovascular disease (death from cardiovascular disease, nonfatal myocardial infarction or nonfatal stroke)

  3 years

Other Outcomes (11)

• Reperfusion procedure for any type of artery

  3 years

• 3. Individual components of the composite of major clinical events of cardiovascular disease

  3 years

• Death from any cause

  3 years

Study Arms (2)

Combination therapy

EXPERIMENTAL

fixed dose single-pill combination of pitavastatin 4mg plus ezetimibe 10mg

Drug: Combination therapy

High intensity statin monotherapy

ACTIVE COMPARATOR

Rosuvastatin 20mg

Drug: High intensity statin monotherapy

Interventions

Combination therapy DRUG

* pitavastatin 4mg * ezetimibe 10mg

Combination therapy

High intensity statin monotherapy DRUG

rosuvastatin 20mg

High intensity statin monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age Requirement:
• Patients aged 18 years or older.
• Glycemic Status:
• Patients who are not taking oral hypoglycemic agents (OHAs) and meet all of the following criteria:
• Fasting glucose less than 126 mg/dL.\*
• HbA1c less than 6.5%.
• Plasma glucose less than 200 mg/dL after 2 hours during a 75 g oral glucose tolerance test (OGTT).\*Note: For fasting glucose, two measurements of 126 mg/dL or greater within 3 months are required for a diagnosis of diabetes.
• Cardiovascular Disease:
• Patients with established atherosclerotic cardiovascular disease, defined as having at least one of the following:
• Coronary Heart Disease (CHD):
• Documented history of myocardial infarction (MI).
• History of coronary revascularization.
• % stenosis of a major epicardial coronary artery confirmed by cardiac catheterization, computed tomography (CT), or coronary angiography.
• Cerebrovascular Disease:
• \>History of stroke of atherosclerotic origin.

You may not qualify if:

• Patient is pregnant or breastfeeding or of childbearing potential.
• Requires concomitant administration of strong inhibitors of CYP3A4 (itraconazole, ketoconazole, protease inhibitors, erythromycin, clarithromycin, telithromycin, and nefazodone) or CYP2C9 (relative contraindication not dependent on CYP450 statins).
• Chronic kidney disease (eGFR \< 30 ml/min/1.73m²) or dialysis-dependent renal failure.
• Uncontrolled hypothyroidism.
• Personal or family history of an inherited muscle disorder.
• History of statin-induced muscle toxicity.
• Alcohol-dependent person.
• Hypersensitivity to statins and ezetimibe.
• Hemodynamic instability at the time of enrollment: cardiogenic shock, refractory ventricular arrhythmia, or congestive heart failure (New York Heart Association class IV) at randomization.
• History of hemorrhagic stroke or intracranial hemorrhage, TIA, or ischemic stroke within the past 6 months.
• Planned surgery requiring discontinuation of statins or ezetimibe within 6 months of randomization.
• Current treatment for active cancer.
• Clinically significant abnormal findings identified at the screening visit, physical examination, laboratory tests, or electrocardiogram that, in the investigator's judgment, may interfere with safe completion of the study.
• Liver disease or biliary obstruction, elevated liver enzymes (ALT or AST \> the upper limit of normal) or elevated total bilirubin (total bilirubin \> 2 times the upper limit of normal) at screening.
• Life expectancy for noncardiac or cardiac causes \< 1 year.

Sponsors & Collaborators

• Korea University Anam Hospital: lead
• Daewon Pharmaceutical Co., Ltd.: collaborator
• Samjin Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Korea University Anam Hospital

Seoul, 02841, South Korea

RECRUITING

Related Publications (22)

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MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Combined Modality Therapy

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Cheol Woong Yu

CONTACT

+82-2-920-5445; ycw717@naver.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 5, 2025
• First Posted: January 10, 2025
• Study Start: April 25, 2025
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

KR (1)